Changes in oxidation status somehow regulate pathogen resistance in plants. The Arabidopsis NPR1, a master regulator of salicylic acid (SA)–mediated defense genes, is held in an inactive multimeric state in the absence of SA and, when SA is released, is converted into a monomer before it is transported into the nucleus where it acts. Tada et al. show that NPR1 is sequestered in the cytoplasm as an oligomer through S-nitrosylation at residue Cys156, which facilitates the oligomerization. Conversely, the SA-induced NPR1 monomerization is catalyzed by reduced thioredoxins. Mutants in both NPR1 Cys156 and thioredoxins compromised NPR1-mediated gene expression and disease resistance; this finding provides a missing link between pathogen-triggered cellular redox changes and gene regulation in plant immunity.